Standardized rating scales such as GAD-7 can be used to assess severity of GAD symptoms.[6] GAD is the most common cause of disability in the workplace in the United States.[7]

In a given year, approximately two percent of American adults and European adults experience GAD.[8][9] Globally about 4% are affected at some point in their life.[1] GAD is seen in women twice as much as men.[10] GAD is also common in individuals with a history of substance abuse and a family history of the disorder.[11] Once GAD develops, it is possible for it become chronic, but can be managed or eliminated with proper treatment.[12]

Contents

Genes are attributed to about a third of general anxiety disorder's variance.[13] Individuals with a genetic predisposition for GAD are more likely to develop GAD, especially in response to a life stressor.[14]

Long-term use of benzodiazepines can worsen underlying anxiety,[15][16] with evidence that reduction of benzodiazepines can lead to a diminishment of anxiety symptoms.[17] Similarly, long-term alcohol use is associated with anxiety disorders,[18] with evidence that prolonged abstinence can result in a disappearance of anxiety symptoms.[19] However, it can take up to two years for anxiety symptoms to return to baseline in about a quarter of people recovering from alcoholism.[20]

In one study in 1988–90, illness in approximately half of patients attending mental health services at British hospital psychiatric clinic, for conditions such as panic disorder or social phobia, was determined to be the result of alcohol or benzodiazepine dependence. In these patients, anxiety symptoms, while worsening initially during the withdrawal phase, disappeared with abstinence from benzodiazepines or alcohol. Sometimes anxiety pre-existed alcohol or benzodiazepine dependence, but the dependence was acting to keep the anxiety disorders going and could progressively make them worse. Recovery from benzodiazepines tends to take a lot longer than recovery from alcohol, but people can regain their previous good health.[20]

Generalized anxiety disorder has been linked to disrupted functional connectivity of the amygdala and its processing of fear and anxiety.[23] Sensory information enters the amygdala through the nuclei of the basolateral complex (consisting of lateral, basal and accessory basal nuclei). The basolateral complex processes the sensory-related fear memories and communicates their threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices.

Another area, the adjacent central nucleus of the amygdala, controls species-specific fear responses in its connections to the brainstem, hypothalamus and cerebellum areas. In those with generalized anxiety disorder, these connections seem less functionally distinct, and there is greater gray matter in the central nucleus. Another difference is that the amygdala areas have decreased connectivity with the insula and cingulate areas that control general stimulus salience, while having greater connectivity with the parietal cortex and prefrontal cortex circuits that underlie executive functions.[23] The latter suggests a compensation strategy for dysfunctional amygdala processing of anxiety. This is consistent with cognitive theories that suggest the use in this disorder of attempts to reduce the involvement of emotions with compensatory cognitive strategies.[23]

Most commonly used exclusion criteria: not sustained by a physical disorder, such as hyperthyroidism, an organic mental disorder (F0) or psychoactive substance-related disorder (F1), such as excess consumption of amphetamine-like substances, or withdrawal from benzodiazepines.[5]

The American Psychiatric Association introduced GAD as a diagnosis in the DSM-III in 1980, when anxiety neurosis was split into GAD and panic disorder.[26] The definition in the DSM-III required uncontrollable and diffuse anxiety or worry that is excessive and unrealistic and persists for 1 month or longer. High rates in comorbidity of GAD and major depression led many commentators to suggest that GAD would be better conceptualized as an aspect of major depression instead of an independent disorder.[27] Many critics stated that the diagnostic features of this disorder were not well established until the DSM-III-R.[28] Since comorbidity of GAD and other disorders decreased with time, the DSM-III-R changed the time requirement for a GAD diagnosis to 6 months or longer.[29] The DSM-IV changed the definition of excessive worry and the number of associated psychophysiological symptoms required for a diagnosis.[27] Another aspect of the diagnosis the DSM-IV clarified was what constitutes a symptom as occurring "often".[30] The DSM-IV also required difficulty controlling the worry to be diagnosed with GAD. The DSM-5 emphasized that excessive worrying had to occur more days than not and on a number of different topics.[28] It has been stated that the constant changes in the diagnostic features of the disorder have made assessing epidemiological statistics such as prevalence and incidence difficult, as well as increasing the difficulty for researchers in identifying the biological and psychological underpinnings of the disorder. Consequently, making specialized medications for the disorder is more difficult as well. This has led to the continuation of GAD being medicated heavily with SSRIs.[28]

Mental disorders are difficult to prevent, but many techniques are available to help relieve and manage anxiety. Many sufferers have found ease by relaxation exercises, deep breathing practice, and meditation.[31] Additionally, avoidance of caffeine may prevent GAD.[32] Avoiding nicotine also can decrease the risk for the development of anxiety disorders including generalized anxiety disorder.[33]

Meta-analysis indicates that both cognitive behavioral therapy (CBT) and medications (such as SSRIs) have been shown to be effective in reducing anxiety. A comparison of overall outcomes of CBT and medication on anxiety did not show statistically significant differences (i.e. they were equally effective in treating anxiety).[citation needed] However, CBT is significantly more effective in reducing depression severity, and its effects are more likely to be maintained in the long term, whereas the effectiveness of pharmacologic treatment tends to lessen if medication is discontinued.[34] A combination of both CBT and medication is generally seen as the most desirable approach to treatment.[35] Use of medication to lower extreme anxiety levels can be important in enabling patients to engage effectively in CBT.

Among the cognitive–behavioral orientated psychotherapies the two main treatments are cognitive behavioral therapy and acceptance and commitment therapy (ACT).[37] Intolerance of uncertainty therapy and motivational interviewing are two new treatments for GAD that are used as either stand-alone treatments or additional strategies that may enhance CBT.[38]

Components of CBT for GAD includes psychoeducation, self-monitoring, stimulus control techniques, relaxation, self-control desensitization, cognitive restructuring, worry exposure, worry behavior modification, and problem-solving. The first step in the treatment of GAD is informing of the patient about the issues and the plan of the solution. The purpose of psychoeducation is to provide some relief, destigmatization of the disorder, motivating, and accomplishing participation by making the patient understand the program of treatment. The purpose of this component is to identify cues that provoke the anxiety. Stimulus control intervention refers to minimizing the stimulus conditions under which worrying occurs. Relaxation techniques lower the patients' stress and thus increase attention to alternatives in feared situations (other than worrying). Deep breathing exercise, progressive muscle relaxation, and applied relaxation fall under the scope of relaxation techniques.[38]

Self-control desensitization involves patients being deeply relaxed before vividly imagining themselves in situations that usually make them anxious and worry until internal anxiety cues are triggered. Patients then imagine themselves coping with the situation and decreasing their anxious response. If anxiety diminishes, they then enter a deeper relaxed state and turn off the scene. The purpose of cognitive restructuring is to shift from a worrisome outlook to a more functional and adaptive perception of the world, the future, and the self. It involves Socratic questioning that leads patients to think through their worries and anxieties so they can realize that alternative interpretations and feelings are more accurate. It also involves behavioral experiments that actually test the validity of both the negative and alternative thoughts in real-life situations. In CBT for GAD, patients also engage in worry exposure exercises during which they are asked to imagine themselves exposed to images of the most feared outcomes. Then they engage in response-prevention instruction that prevents them from avoiding the image and motivates alternative outcomes to the feared stimulus. The goals of worry exposure are habituation and reinterpretation of the meaning of the feared stimulus. Worry behavior prevention requires patients to monitor the behaviors that caused them worry and are then asked to prevent themselves from engaging in them. Instead, they are encouraged to use other coping mechanisms learned earlier in the treatment. Finally, problem solving focuses on dealing with current problems through a problem-solving approach: (1) definition of the problem, (2) formulation of goals, (3) creation of alternative solutions, (4) decision-making, and (5) implementing and verifying the solutions.[38]

There is little debate regarding the effectiveness of CBT for GAD. However, there is still room for improvement because only about 50% of those who complete treatments achieve higher functioning or recovery after treatment. Therefore, there's a need for enhancement of current components of CBT.[38] CBT usually helps one-third of the patients substantially, whilst another third does not respond at all to treatment.[41]

Acceptance and commitment therapy (ACT) is a behavioral treatment based on acceptance-based models. ACT is designed with the purpose to target three therapeutic goals: (1) reduce the use of avoiding strategies intended to avoid feelings, thoughts, memories, and sensations; (2) decreasing a person's literal response to their thoughts (e.g., understanding that thinking "I'm hopeless" does not mean that the person's life is truly hopeless), and (3) increasing the person's ability to keep commitments to changing their behaviors. These goals are attained by switching the person's attempt to control events to working towards changing their behavior and focusing on valued directions and goals in their lives as well as committing to behaviors that help the individual accomplish those personal goals.[42] This psychological therapy teaches mindfulness (paying attention on purpose, in the present, and in a nonjudgmental manner) and acceptance (openness and willingness to sustain contact) skills for responding to uncontrollable events and therefore manifesting behaviors that enact personal values.[43] Like many other psychological therapies, ACT works best in combination with pharmacology treatments.[citation needed]

Intolerance of uncertainty therapy (IUT) refers to a consistent negative reaction to uncertain and ambiguous events regardless of their likelihood of occurrence. IUT is used as a stand-alone treatment for GAD patients. Thus, IUT focuses on helping patients in developing the ability to tolerate, cope with and accept uncertainty in their life in order to reduce anxiety. IUT is based on the psychological components of psychoeducation, awareness of worry, problem-solving training, re-evaluation of the usefulness of worry, imagining virtual exposure, recognition of uncertainty, and behavioral exposure. Studies have shown support for the efficacy of this therapy with GAD patients with continued improvements in follow-up periods.[38]

A promising innovative approach to improving recovery rates for the treatment of GAD is to combine CBT with motivational interviewing (MI). Motivational interviewing is a strategy centered on the patient that aims to increase intrinsic motivation and decrease ambivalence about change due to the treatment. MI contains four key elements: (1) express empathy, (2) heighten dissonance between behaviors that are not desired and values that are not consistent with those behaviors, (3) move with resistance rather than direct confrontation, and (4) encourage self-efficacy. It is based on asking open-ended questions and listening carefully and reflectively to patients' answers, eliciting "change talk", and talking with patients about the pros and cons of change. Some studies have shown the combination of CBT with MI to be more effective than CBT alone.[38]

Lifestyle

Lifestyle factors including: stress management, stress reduction, relaxation, exercise, sleep hygiene, caffeine, and alcohol can influence the persistence of anxiety. Stress is a factor that can trigger anxiety. Therefore, keeping stress levels low through stress management, stress reduction, and relaxation may be beneficial. Physical activity has shown to have a positive impact whereas low physical activity may be a risk factor for anxiety disorders.[44]

Pharmaceutical treatments for GAD include selective serotonin reuptake inhibitors (SSRIs).[40] These are the preferred first line of treatment.[45] FDA approved SSRIs used for this purpose include escitalopram[46] and paroxetine.[47] However, guidelines suggest using sertraline first due to its cost-effectiveness compared to other SSRIs used for generalized anxiety disorder and a lower risk of withdrawal compared to SNRIs. If sertraline is found to be ineffective, then it is recommended to try another SSRI or SNRI.[48]

Common side effects include nausea, sexual dysfunction, headache, diarrhea, constipation, restlessness, increased risk of suicide in young adults and adolescents,[49]among others. Sexual side effects, weight gain, and higher risk of withdrawal are more common in paroxetine than escitalopram and sertraline.[50] In older populations or those taking concomitant medications that increase risk of bleeding , SSRIs may further increase the risk of bleeding.[48] Overdose of an SSRI or concomitant use with another agent that causes increased levels of serotonin can result in serotonin syndrome, which can be life threatening.

Serotonin norepinephrine reuptake inhibitors

First line pharmaceutical treatments for GAD also include serotonin-norepinephrine reuptake inhibitors (SNRIs).[51] FDA approved SNRIs used for this purpose include duloxetine (Cymbalta) and venlafaxine (Effexor).[52][53] While SNRIs have similar efficacy as SSRIs,[54] many psychiatrists prefer to use SSRIs first in the treatment of Generalized Anxiety Disorder.[55][56][57][52] The slightly higher preference for SSRIs over SNRIs as a first choice for treatment of anxiety disorders may have been influenced by the observation of poorer tolerability of the SNRIs in comparison to SSRIs in systematic reviews of studies of depressed patients.[58][59][60] Duloxetine is also indicated for the treatment of chronic musculoskeletal pain and neuropathic pain associated with diabetes mellitus,[61] and may be a good option for patients with both conditions.[57] Side effects common to both SNRIs include anxiety, restlessness, nausea, weight loss, insomnia, dizziness, drowsiness, sweating, dry mouth, sexual dysfunction and weakness.[62] In comparison to SSRIs, the SNRIs have a higher prevalence of the side effects of insomnia, dry mouth, nausea and high blood pressure.[63][62] Both SNRIs have the potential for discontinuation syndrome after abrupt cessation, which can precipitate symptoms including motor disturbances and anxiety and may require tapering.[61][64] Like other serotonergic agents, SNRIs have the potential to cause serotonin syndrome, a potentially fatal systemic response to serotonergic excess that causes symptoms including agitation, restlessness, confusion, tachycardia, hypertension, mydriasis, ataxia, myoclonus, muscle rigidity, diaphoresis, diarrhea, headache, shivering, goose bumps, high fever, seizures, arrhythmia and unconsciousness.[65] SNRIs like SSRIs carry a black box warning for suicidal ideation, but it is generally considered that the risk of suicide in untreated depression is far higher than the risk of suicide when depression is properly treated.[66]

Benzodiazepines are most often prescribed to people with generalized anxiety disorder. Research suggests that these medications give some relief, at least in the short term. However, they carry some risks, mainly impairment of both cognitive and motor functioning, and psychological and physical dependence that makes it difficult for patients to stop taking them. It has been noted that people taking benzodiazepines are not as alert on their job or at school. Additionally, these medications may impair driving and they are often associated with falls in the elderly, resulting in hip fractures. These shortcomings make the use of benzodiazepines optimal only for short-term relief of anxiety.[67] CBT and medication are of comparable efficacy in the short-term but CBT has advantages over medication in the longer term.[68]

Pregabalin (Lyrica) acts on the voltage-dependent calcium channel to decrease the release of neurotransmitters such as glutamate, norepinephrine and substance P. Its therapeutic effect appears after 1 week of use and is similar in effectiveness to lorazepam, alprazolam and venlafaxine but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance and additionally, unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment. It also has a low potential for abuse and dependency and may be preferred over the benzodiazepines for these reasons.[71][72] The anxiolytic effects of pregabalin appear to persist for at least six months continuous use, suggesting tolerance is less of a concern; this gives pregabalin an advantage over certain anxiolytic medications such as benzodiazepines.[73]

Gabapentin (Neurontin), a closely related medication to pregabalin with the same mechanism of action, has also demonstrated effectiveness in the treatment of GAD,[74] though unlike pregabalin, it has not been approved specifically for this indication. Nonetheless, it is likely to be of similar usefulness in the management of this condition, and by virtue of being off-patent, it has the advantage of being significantly less expensive in comparison.[75] In accordance, gabapentin is frequently prescribed off-label to treat GAD.[76]

5-HT1A receptorpartial agonists, such as buspirone. Buspirone is an FDA approved first line agent, to be used if SSRI/SNRIs are contraindicated or fail as a treatment. Like the SSRI/SNRIs buspirone has a 2-4 week delayed onset of action and a maximum benefit seen at 4–6 weeks. Common side effects include dizziness, nausea, and headache. This is a well-tolerated drug with no sedation or sexual side effects, which are commonly seen with SSRI/SNRIs. However, buspirone is not as effective in patients who have been previously treated with benzodiazepines.[77]

In the National Comorbidity Survey (2005), 58 percent of patients diagnosed with major depression were found to have an anxiety disorder; among these patients, the rate of comorbidity with GAD was 17.2 percent, and with panic disorder, 9.9 percent. Patients with a diagnosed anxiety disorder also had high rates of comorbid depression, including 22.4 percent of patients with social phobia, 9.4 percent with agoraphobia, and 2.3 percent with panic disorder.[citation needed] A longitudinal cohort study found 12% of the 972 participants had GAD comorbid with MDD.[78] Accumulating evidence indicates that patients with comorbid depression and anxiety tend to have greater illness severity and a lower treatment response than those with either disorder alone.[79] In addition, social function and quality of life are more greatly impaired.

For many, the symptoms of both depression and anxiety are not severe enough (i.e. are subsyndromal) to justify a primary diagnosis of either major depressive disorder (MDD) or an anxiety disorder. However, dysthymia is the most prevalent comorbid diagnosis of GAD clients. Patients can also be categorized as having mixed anxiety-depressive disorder, and they are at significantly increased risk of developing full-blown depression or anxiety.[citation needed]

Various explanations for the high comorbidity between GAD and depressive disorders have been suggested, including genetic pleiotropy, meaning that GAD and nonbipolar depression might represent different phenotypic expressions of a common etiology.[26]

Those with GAD have a lifetime comorbidity prevalence of 30% to 35% with alcohol use disorder and 25% to 30% for another substance use disorder.[80] People with both GAD and a substance use disorder also have a higher lifetime prevalence for other comorbidities.[80] A study found that GAD was the primary disorder in slightly more than half of the 18 participants that were comorbid with alcohol use disorder.[81]

In addition to coexisting with depression, research shows that GAD often coexists with conditions associated with stress, such as irritable bowel syndrome.[82] Patients with GAD can sometimes present with symptoms such as insomnia or headaches as well as pain, cardiac events and interpersonal problems.[83]

United States: approx. 3.1 percent of people age 18 and over in a given year (9.5 million)[8]

The usual age of onset is variable, from childhood to late adulthood, with the median age of onset being approximately 31[87] and mean age of onset is 32.7.[88] Most studies find that GAD is associated with an earlier and more gradual onset than the other anxiety disorders.[89] The prevalence of GAD in children is approximately 3%; the prevalence in adolescents is reported as high as 10.8%.[90] When GAD appears in children and adolescents, it typically begins around 8 to 9 years of age.[91]

Populations with a higher rate of diagnosis of GAD are individuals that are traditionally oppressed. This includes individuals with low and middle socio-economic status, separated, divorced, and widowed individuals. Women are twice as likely to develop GAD as men. This is primarily because women are more likely than men to live in poverty, be subject to discrimination, and be sexually and physically abused.[92] African Americans have significantly higher odds of enduring GAD and the disorder often manifests itself in different patterns.[93][94] Other populations that are more diagnosed with GAD are those who live alone, those with a low level of education, and the unemployed.[95] GAD is also common in the elderly population.[96]

Compared to the general population, patients with internalizing disorders such as depression, generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD) have higher mortality rates, but die of the same age-related diseases as the population, such as heart disease, cerebrovascular disease and cancer.[97]

A study on comorbidity of GAD and other depressive disorders has shown that treatment is not more or less effective when there is some sort of comorbidity of another disorder.[98] The severity of symptoms did not affect the outcome of the treatment process in these cases.

^Baldwin, David S.; Allgulander, Christer; Bandelow, Borwin; Ferre, Francisco; Pallanti, Stefano (October 2012). "An international survey of reported prescribing practice in the treatment of patients with generalised anxiety disorder". The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry. 13 (7): 510–516. doi:10.3109/15622975.2011.624548. ISSN1814-1412. PMID22059936.